AB0696 Prevalence and clinical associations of different autoantibodies in the Reuma.pt systemic sclerosis cohort: is it all really set in stone?
Authors: E. Dourado, R. Freitas, P. Martins, L. Saraiva, T. Santiago, F. Guimarães, E. Costa, D. Esperança Almeida, S. P. Dinis, A. S. Pinto, A. Daniel, I. Genrinho, M. Couto, M. Rodrigues, M. J. Salvador, A. C. Duarte, A. Cordeiro, M. J. Santos, J. E. Fonseca, C. Resende, I. Cordeiro
Journal: Annals of the Rheumatic Diseases (2022)

Background Different autoantibodies (Ab) have been associated with distinct systemic sclerosis (SSc) phenotypes. Most of these associations have not been confirmed in Portuguese patients. Objectives To evaluate SSc immuno-clinical associations in the Rheumatic Diseases Portuguese Register (Reuma.pt) cohort. Methods Multicentre open cohort study including adult SSc patients registered in Reuma.pt up to February 2021. The associations between Ab expression and clinical data were established using Chi-Square, Fischer’s Exact or Mann-Whitney U tests. The Bonferroni correction for multiple comparisons was applied to get α≤0.05. Definite associations were defined by p≤0.002, and likely associations by p≤0.05. Results 1080 patients were included, with a mean age and disease duration of 60.2±14.6 and 12.4±10.0 years, respectively. Most were females (87.5%) and had white European ancestry (WEA, 93.2%). The most common disease subtypes were limited cutaneous (lcSSc, 57.4%), diffuse cutaneous (dcSSc, 17.7%), and very early diagnosis of SSc (VEDOSS, 12.3%). Most patients expressed antinuclear Ab (ANA, 93.4%), and the most frequent were anti-centromere (ACA, 54.6%), anti-topoisomerase I (Scl70, 21.8%), and anti-Pm/Scl Ab (PmScl, 4.7%). ACA had definite positive associations with female sex, older age at diagnosis, lcSSc, lower modified Rodnan skin score (mRSS, median 0 vs 4), and isolated sclerodactyly, and likely associations with a higher diagnosis delay, WEA and VEDOSS. ACA had definite inverse associations with flexion contractures (FC), myositis, digital ulcers (DU), and interstitial lung disease (ILD), and likely inverse associations with pitting scars (PS) and oesophageal involvement (OI). Scl70 had definite positive associations with male sex, dcSSc, higher mRSS, FC, DU, PS, ILD, and OI, and likely associations with younger age at diagnosis, tendon friction rubs, active scleroderma pattern in capillaroscopy, and heart involvement. PmScl had a definite association with myositis and likely associations with male sex, calcinosis, joints involvement, and ILD. Anti-U1RNP Ab had definite associations with younger age at diagnosis, MCTD and myositis, and likely associations with a lower diagnosis delay, African ancestry and joint involvement. Anti-RNA polymerase III Ab (RP3) had likely associations with higher mRSS and renal involvement. Anti-U3RNP Ab had a definite association with dcSSc and likely associations with calcinosis and renal involvement. Anti-Th/To Ab had likely associations with male sex and myositis. Anti-Ku Ab had likely associations with systemic lupus erythematosus and mixed connective tissue disease (MCTD) overlap syndromes. Conclusion There was a higher prevalence of ACA and PmScl compared to other cohorts, most likely due to the high proportion of WEA patients. Most immuno-clinical associations described in the literature apply, including ACA with lcSSc and Scl70 with dcSSc, DU, PS and ILD. However, Scl70+ patients did not have an increased risk of renal involvement, and ACA+ patients did not have an increased risk for calcinosis, PAH or OI, contrary to what was described in the literature. New findings included the association of PmScl with ILD and Scl70 with an active pattern in capillaroscopy. Also, anti-U3RNP+ and Th/To+ patients did not have an increased risk of ILD or PAH, contrarily to what was previously reported. These nuances may be specific to the Portuguese SSc population or signal previously reported associations as geographically specific. Disclosure of Interests None declared